Organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses

doi:10.1016/j.nuclcard.2006.08.016

Journal of Nuclear Cardiology

Volume 13, Issue 6, November 2006, Pages 779-790

https://doi.org/10.1016/j.nuclcard.2006.08.016 Get rights and content

Background

Technetium 99m N-DBODC5 is a new myocardial perfusion tracer shown to exhibit high heart uptake and rapid liver clearance in normal rats. The objectives of this canine study were (1) to compare the organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 with Tc-99m sestamibi over a period of 3 hours in a more clinically relevant large animal species and (2) to compare the myocardial uptake of Tc-99m N-DBODC5 with thallium 201 when co-injected during vasodilator stress in dogs with coronary stenoses.

Methods and Results

At peak adenosine-induced hyperemia, 10 dogs with critical left anterior descending artery stenoses received either Tc-99m N-DBODC5 (n = 6) or Tc-99m sestamibi (n = 4) and microspheres, followed by serial imaging and blood sampling over a period of 3 hours. Another 14 dogs with either critical (n = 7) or mild (n = 7) left anterior descending artery stenoses underwent simultaneous injection of Tc-99m N-DBODC5, Tl-201, and microspheres during peak vasodilator stress. Like sestamibi, Tc-99m N-DBODC5 showed good myocardial uptake with slow washout and minimal redistribution over a period of 3 hours (P = not significant); however, Tc-99m N-DBODC5 cleared more rapidly from the liver (heart-lung ratio at 30 minutes, 0.92 ± 0.11 versus 0.51 ± 0.05; P < .05). When injected during hyperemic flow, the myocardial extraction plateau for Tc-99m N-DBODC5 was lower than that for Tl-201 and was intermediate between Tc-99m sestamibi and Tc-99m tetrofosmin.

Conclusions

Excellent organ biodistribution and myocardial uptake and clearance kinetic properties, combined with rapid liver clearance and a favorable flow-extraction relationship, make Tc-99m N-DBODC5 a very promising new myocardial perfusion imaging agent.

Section snippets

Methods

All experiments were performed with the approval of the University of Virginia Animal Care and Use Committee (Charlottesville, Va) in compliance with the position of the American Heart Association on the use of research animals.

Hemodynamic parameters

The hemodynamic parameters from the protocol 1 experiments are summarized in Table 1. Adenosine stress resulted in a fall in mean arterial blood pressure, a rise in heart rate, and an increase in the nonstenotic LCx flow. The stenotic LAD flow fell slightly during the vasodilator infusion. There was a greater than 5-fold flow disparity between the stenotic LAD and normal LCx beds at peak adenosine vasodilatation when the tracers were injected in both Tc-99m N-DBODC5 and Tc-99m sestamibi groups (

Discussion

The quest for better radionuclide perfusion imaging agents, which track myocardial blood flow over a wide range with minimal splanchnic uptake, has been recognized to be of great importance in clinical nuclear cardiology.²⁰ Over the past decade, Tc-99m–labeled myocardial perfusion tracers that use lipophilic, cationic molecules such as Tc-99m sestamibi and Tc-99m tetrofosmin have advanced the field of noninvasive diagnostic evaluation and risk stratification of patients with known or

Acknowledgment

The authors have indicated they have no financial conflicts of interest.

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: This experimental study was funded by a generous research grant from Nihon Medi-Physics Co, Ltd.

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Original articleOrgan biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses

Background

Methods and Results

Conclusions

Section snippets

Methods

Hemodynamic parameters

Discussion

Acknowledgment

J Nucl Cardiol

Prog Cardiovasc Dis

Semin Nucl Med

Lancet

Am Heart J

Am Heart J

A class of asymmetrical nitrido 99mTc heterocomplexes as heart imaging agents with improved biological properties

Nucl Med Commun

Synthesis and biologic evaluation of monocationic asymmetric 99mTc-nitride heterocomplexes showing high heart uptake and improved imaging properties

J Nucl Med

99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with 99mTc-sestamibi and 99mTc-tetrofosmin in rats

J Nucl Med

Technetium-99m hexakis 2-methoxyisobutyl isonitrile: human biodistribution, dosimetry, safety, and preliminary comparison to thallium-201 for myocardial perfusion imaging

J Nucl Med

Technetium-99m-1,2-bis[bis(2-ethoxyethyl) phosphino]ethane: human biodistribution, dosimetry and safety of a new myocardial perfusion imaging agent

J Nucl Med

Biokinetics of technetium-99m-tetrofosmin: myocardial perfusion imaging agent: implications for a one-day imaging protocol

J Nucl Med

Evaluation of techniques for the elimination of “hot” bladder artifacts in SPECT of the pelvis

J Nucl Med

Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera

J Nucl Med

Original article
Organ biodistribution and myocardial uptake, washout, and redistribution kinetics of Tc-99m N-DBODC5 when injected during vasodilator stress in canine models of coronary stenoses

^99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearance: comparison with ^99mTc-sestamibi and ^99mTc-tetrofosmin in rats